I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Principles of Neural Science

Double-stranded RNA-mediated interference (RNAi) is a simple and rapid method of silencing gene expression in a range of organisms. The silencing of a gene is a consequence of degradation of RNA into short RNAs that activate ribonucleases to target homologous mRNA. The resulting phenotypes either are identical to those of genetic null mutants or resemble an allelic series of mutants. Specific gene silencing has been shown to be related to two ancient processes, cosuppression in plants and quelling in fungi, and has also been associated with regulatory processes such as transposon silencing, antiviral defense mechanisms, gene regulation, and chromosomal modification. Extensive genetic and biochemical analysis revealed a two-step mechanism of RNAi-induced gene silencing. The first step involves degradation of dsRNA into small interfering RNAs (siRNAs), 21 to 25 nucleotides long, by an RNase III-like activity. In the second step, the siRNAs join an RNase complex, RISC (RNA-induced silencing complex), which acts on the cognate mRNA and degrades it. Several key components such as Dicer, RNA-dependent RNA polymerase, helicases, and dsRNA endonucleases have been identified in different organisms for their roles in RNAi. Some of these components also control the development of many organisms by processing many noncoding RNAs, called micro-RNAs. The biogenesis and function of micro-RNAs resemble RNAi activities to a large extent. Recent studies indicate that in the context of RNAi, the genome also undergoes alterations in the form of DNA methylation, heterochromatin formation, and programmed DNA elimination. As a result of these changes, the silencing effect of gene functions is exercised as tightly as possible. Because of its exquisite specificity and efficiency, RNAi is being considered as an important tool not only for functional genomics, but also for gene-specific therapeutic activities that target the mRNAs of disease-related genes.

/pdf/rna-interference-biology-mechanism-and-applications-ww381qhd6t.pdf

RNA Interference: Biology, Mechanism, and Applications

Central pattern generators and the control of rhythmic movements

Experimental Psychology Its Scope and Method. IV. Learning and Memory. By Jean-Francois Le Ny, G. De Montpellier, G. Oleron and Cesar Flores. Translated by Louise Elkington. Edited by P. Fraisse and Jean Piaget. Pp. viii + 376. (Routledge and Kegan Paul: London, April 1970.) 80s.

Learning and Memory

The Study of Instinct

A role for the NO-cGMP pathway in mediating chemosensory activation of feeding is suggested by intense NADPH diaphorase staining observed in nerve fibers that project from sensory cells in the lips to the CNS and by the presence in the CNS of a NO-activated guanylyl cyclase. In preparations reduced to isolated lips and CNS, intracellular recordings were made from motoneurons driven by the interneurons of the central pattern generator (CPG) for feeding. Fictive feeding in such preparations can be recorded from these motoneurons following the application of sucrose to the lips. Sucrose activation of fictive feeding is inhibited by the NO scavenger hemoglobin, the NO synthase inhibitor N omega-Nitro-L-Arginine Methyl Ester (L-NAME) and by methylene blue, an inhibitor of guanylyl cyclase. Fictive feeding in isolated lip-CNS preparations can be activated without sucrose by superfusion of NO donor molecules such as SNAP and hydroxylamine and by the nonhydrolyzable analog of cGMP, 8-bromo-cGMP. The feeding CPG can also be activated centrally by depolarizing a modulatory interneuron, the slow oscillator (SO). When the CPG is activated in this way, fictive feeding is not susceptible to inhibition by hemoglobin, the most potent of the inhibitors of sucrose-activated fictive feeding. Behavioral experiments on intact snails confirm the findings from in vitro experiments and show that hemoglobin prevents feeding and methylene blue significantly delays the onset of feeding. These results indicate (1) that NO is a putative chemosensory transmitter in the snail L. stagnalis, (2) that the NO-cGMP pathway can mediate chemosensory activation of specific patterns of centrally generated behavior, (3) that NO is not involved in transmission within the central network of neurons responsible for the behavior, and more generally (4) that a freely diffusing and highly reactive gaseous signalling molecule can have restricted and specific behavioral functions.

https://www.jneurosci.org/content/jneuro/15/11/7653.full.pdf

Behavioral Role for Nitric Oxide in Chemosensory Activation of Feeding in a Mollusc

We show that appetitive and aversive conditioning can be analyzed at the cellular level in the well-described neural circuitries underlying rhythmic feeding and respiration in the pond snail, Lymnaea stagnalis. To relate electrical changes directly to behavior, the snails were first trained and the neural changes recorded at multiple sites in reduced preparations made from the same animals. Changes in neural activity following conditioning could be recorded at the level of motoneurons, central pattern generator interneurons and modulatory neurons. Of significant interest was recent work showing that neural correlates of long-term memory could be recorded in the feeding network following single-trial appetitive chemical conditioning. Available information on the synaptic connectivity and transmitter content of identified neurons within the Lymnaea circuits will allow further work on the synaptic and molecular mechanisms of learning and memory.

/pdf/a-systems-approach-to-the-cellular-analysis-of-associative-28ppzxlaw2.pdf

A systems approach to the cellular analysis of associative learning in the pond snail Lymnaea.

The nitric oxide (NO)-cGMP signaling pathway is implicated in an increasing number of experimental models of plasticity. Here, in a behavioral analysis using one-trial appetitive associative conditioning, we show that there is an obligatory requirement for this pathway in the formation of long-term memory (LTM). Moreover, we demonstrate that this requirement lasts for a critical period of ~5 hr after training. Specifically, we trained intact specimens of the snail Lymnaea stagnalis in a single conditioning trial using a conditioned stimulus, amyl-acetate, paired with a salient unconditioned stimulus, sucrose, for feeding. Long-term associative memory induced by a single associative trial was demonstrated at 24 hr and shown to last at least 14 d after training. Tests for LTM and its dependence on NO were performed routinely 24 hr after training. The critical period when NO was needed for memory formation was established by transiently depleting it from the animals at a series of time points after training by the injection of the NO-scavenger 2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl 3-oxide (PTIO).By blocking the activity of NO synthase and soluble guanylyl cyclase enzymes after training, we provided further evidence that LTM formation depends on an intact NO-cGMP pathway. An electrophysiological correlate of LTM was also blocked by PTIO, showing that the dependence of LTM on NO is amenable to analysis at the cellular level in vitro. This represents the first demonstration that associative memory formation after single-trial appetitive classical conditioning is dependent on an intact NO-cGMP signaling pathway.

https://www.jneurosci.org/content/jneuro/22/4/1414.full.pdf

Critical Time-Window for NO–cGMP-Dependent Long-Term Memory Formation after One-Trial Appetitive Conditioning

Role of Delayed Nonsynaptic Neuronal Plasticity in Long-Term Associative Memory

Transfer of snails from distilled water to solutions of sucrose or maltose stimulated feeding behaviour. As the concentrations were increased from 10 −5 mol l −1 to 10 −1 mol l −1 the proportions of snails showing feeding movements and the median rate of feeding both increased until at 10 −3 mol 1 −1 they reached a plateau. At higher concentrations (10 −1 mol l −1 ), maltose, but not sucrose, reduced the proportion of feeding snails and median feeding rate to values occurring at 10 −5 mol 1 −1 . Increases in median feeding rate were due to an increase in the regularity of the feeding rhythm rather than increases in the maximum rates of feeding. Sugars and tactile stimuli were applied to putative sensory structures (interior of the buccal mass, lips and tentacles) in two types of semi-intact preparation whilst intracellular recordings were made from feeding motoneurones (1, 3, 4, 5 and 7 cells) and higher-order interneurones (Cerebral Giant Cells, CGCs, and the Slow Oscillator, SO). Both types of sensory stimuli applied to the lip-tentacle preparation produced strong activation of the CGCs but only long latency weak excitation of motoneurones with no clear initiation of synaptic inputs from central pattern generating (CPG) interneurones. In a more complex lip-tentacle-buccal mass preparation the evoked responses to sugars were comparable to those in the intact snail. Initiation of motoneuronal activity or increased frequency of activity was observed. This was due to increased CPG synaptic inputs as well as activation of a modulatory interneurone, the SO. Multiple sensory pathways from the periphery, present only in the lip-tentacle-buccal mass preparation, were necessary for sensory initiation of the feeding rhythm. The results support the hypothesis that multimodal sensory inputs are likely to be involved in the initiation or modulation of feeding in Lymnaea and act at several levels in the system. Note:

György Kemenes

Papers

Behavioral Role for Nitric Oxide in Chemosensory Activation of Feeding in a Mollusc

A systems approach to the cellular analysis of associative learning in the pond snail Lymnaea.

Critical Time-Window for NO–cGMP-Dependent Long-Term Memory Formation after One-Trial Appetitive Conditioning

Role of Delayed Nonsynaptic Neuronal Plasticity in Long-Term Associative Memory

Chemical and tactile inputs to the lymnaea feeding system: effects on behaviour and neural circuitry